DNA sequence context greatly affects the accuracy of bypass across an ultraviolet light 6-4 photoproduct in mammalian cells
| Autor: | Pola Shriber, Nicholas E. Geacintov, Tamar Paz-Elizur, Zvi Livneh, Yael Leitner-Dagan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
DNA damage
DNA polymerase DNA repair Ultraviolet Rays Health Toxicology and Mutagenesis Pyrimidine dimer medicine.disease_cause Article chemistry.chemical_compound Mice Species Specificity Genetics Ultraviolet light medicine Animals Humans Molecular Biology Cell Line Transformed Mutation biology DNA synthesis Molecular biology chemistry Pyrimidine Dimers biology.protein DNA DNA Damage |
| Popis: | Translesion DNA synthesis (TLS) is a DNA damage tolerance mechanism carried out by low-fidelity DNA polymerases that bypass DNA lesions, which overcomes replication stalling. Despite the miscoding nature of most common DNA lesions, several of them are bypassed in mammalian cells in a relatively accurate manner, which plays a key role maintaining a low mutation load. Whereas it is generally agreed that TLS across the major UV and sunlight induced DNA lesion, the cyclobutane pyrimidine dimer (CPD), is accurate, there were conflicting reports on whether the same is true for the thymine–thymine pyrimidine–pyrimidone(6-4) ultraviolet light photoproduct (TT6-4PP), which represents the second most common class of UV lesions. Using a TLS assay system based on gapped plasmids carrying site-specific TT6-4PP lesions in defined sequence contexts we show that the DNA sequence context markedly affected both the extent and accuracy of TLS. The sequence exhibiting higher TLS exhibited also higher error-frequency, caused primarily by semi-targeted mutations, at the nearest nucleotides flanking the lesion. Our results resolve the discrepancy reported on TLS across TT6-4PP, and suggest that TLS is more accurate in human cells than in mouse cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|